Previous studies have identified the prostate stem cell antigen (PSCA) gene rs2294008 C > T and rs2976392 G > A polymorphisms to be associated with the risk of gastric cancer, the results of which are inconsistent. The present study aimed to evaluate the association between the two polymorphisms and the gastric cancer risk in the Chinese population. A hospital-based case–control study was conducted on 549 cases and 592 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the association of the two polymorphisms on the gastric cancer risk. We found that both rs2294008 (CT vs. CC, OR = 1.55, 95% CI = 1.20–1.99, P<0.001 and CT+TT vs. CC, OR = 1.38, 95% CI = 1.09–1.74, P=0.008) and rs2976392 (GA vs. GG, OR = 1.61, 95% CI = 1.25–2.07, P<0.001 and GA+AA vs. GG, OR = 1.52, 95% CI = 1.20–1.92, P<0.001) were associated with an increased gastric cancer. In the combined analysis of the two polymorphisms, subjects with more than one risk genotype have a significantly increased risk of gastric cancer (OR = 1.38, 95% CI = 1.09–1.75, P=0.008) in comparison with those without any risk genotypes. In conclusion, our findings verified that the PSCA gene rs2294008 and rs2976392 polymorphisms were both significantly associated with an increased risk of gastric cancer in the Chinese population. Well-designed functional studies are to be warranted to confirm these findings.